Lineage dynamics of invasive Escherichia coli isolates in the Netherlands from 1975 to 2021: a retrospective...

Escherichia coli is a common cause of invasive infections such as bloodstream and cerebrospinal fluid infections in neonates. Strains positive for the K1 capsule are considered the most common cause of such neonatal invasive infections. This assumption of K1 dominance, and indeed the population genomics of E coli causing invasive infections in general is largely unstudied. We aimed to provide a comprehensive characterisation of this pathogen population using a longitudinal isolate collection.

In this analysis we report the findings of the SENTINEL study, a longitudinal genomic analysis of 1790 invasive E coli isolates collected mainly from newborns in the Netherlands between 1975 and 2021 by the Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Centre, Amsterdam, Netherlands. The dataset included all bacterial strains cultured from cerebrospinal fluid or blood in cases of (clinical) bacterial meningitis (1976 to 1980). In 1981 the criteria were expanded to include neonates (aged ≤4 weeks) with E coli sepsis, and from July, 2016 all infants younger than 1 year with E coli sepsis were included. All isolates were sequenced using either the HiSeq 2500 or HiSeq 4000 platforms (Illumina, San Diego, CA, USA). We confirmed species and identified sequence types (STs), detected antimicrobial resistance genes, virulence genes, and the presence of K1 capsule, and characterised the dynamics of these factors over time.

Our data show a highly dynamic bacterial population that is entirely unaffected by antimicrobial resistance determinants. Key pathogen population fluctuations include the complete disappearance of the dominant lineage ST567 and the swapping of dominant ST95 clones from a single serotype O18:H7 clone to two distinct serotype O1:H7 clones, with changes in virulence factors including major fimbrial adhesins. These findings, combined with only 58·8% (1053 of 1790) prevalence in K1-expressing isolates in the entire study population, point to host-pathogen interaction and immune selection pressures as key drivers of bacterial population dynamics in this largely antimicrobial-naive population.

Our data show the vital need for ongoing genomic surveillance of microbial pathogen populations to guide appropriate intervention strategies. Additionally, genomic insights of a pathogen population from one specific disease syndrome or patient population cannot always be generalised across other cohorts.

Wellcome Antimicrobial and Antimicrobial Resistance Doctoral Training Programme and the National Institute for Health and Care Research Birmingham Biomedical Research Centre.